Meloxicam (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) is a new generation non-steroidal anti-inflammatory drug, which has strong pharmacological effects like anti-inflammation, analgesia, antipyresis etc. It is the first marketed COX-2 inhibitor. However, studies suggest that there exists metabolic polymorphism on the in vivo pharmacokinetic behavior of meloxicam in Chinese subjects. It is probably caused by the variation in the degree of first-pass metabolism in the Chinese, but overall slow metabolism is the major type. If certain injection is administered in combination with oral medication at the early stage of treatment to rapidly reach the peak concentration, significant effects will be achieved in improving therapeutic effect and alleviating the patients' suffering. On the other hand, the anti-inflammatory effects of eye drops made from non-steroidal anti-inflammatory drugs are exactly the same with those of topically applied corticosteroid eye drops, and the non-steroidal anti-inflammatory drugs have strong ocular permeability in eyes; while the side effects of long-term use of corticosteroid can be avoided. A prior patent (publication No. CN1301177A) disclosed that meloxicam can be used for treating ocular inflammation, and it suggested that meloxicam eye drops have excellent effects. However, the formulation provided by that patent contains surfactants such as Tween-80; due to the limitations from the intrinsic nature of the surfactants, there is concern about its dosage and safety.
Cyclodextrin (CD) is a new pharmaceutical excipient, which can clathrate various pharmaceutical active ingredients at the molecular level, therefore impart them new physical and chemical properties, wherein the characteristic of increasing the solubility of the insoluble and poorly soluble drugs makes cyclodextrin attract much attention in the area of liquid pharmaceutical preparations. Among them, hydroxypropyl-β-cyclodextrin (HP-β-CD), which is a hydroxyalkyl derivative of β-CD, is the first intravenously injectable β-CD derivative approved by FDA in US. The itraconazole injection containing HP-β-CD produced by Johnson & Johnson has been marketed. The sulfobutylether-β-cyclodextrin (SBE-β-CD) developed by Cydex Corp., US in 1990s is the product of substitution reaction between β-CD and 1,4-butane sultone. An antipsychotic agent named Ziprasidone injection, which has SBE-β-CD as the clathrate material, has been successfully developed by Pfizer and marketed in the U.S. The two cyclodextrins show promising applications in the preparation of liquid medicine.
Due to their significant advantages, polymers are preliminarily replacing the surfactants in the area of liquid preparation for external use. It prevents the potential toxicity, irritation, hemolysis and other side effects of the surfactants, and also greatly contributes to improving the solubility and stability of the drugs. At the same time, the particular viscosity of polymers has special significance to the eye drops. It may not only reduce the irritation, but also increase the residence time of the drug solution in the eyes.